L-asparaginase, has been shown by other workers to produce remissions in certain mouse and human leukemias and in certain lymphomas. More recently it has been shown to interfere with aspects of the immune response in mice. The response to the enzyme appears to involve a nutritional requirement of some lymphocytes for the amino acid, asparagine. Asparaginase is of limited usefulness: 1) asparaginase is inactive against cells which contain high levels of asparagine synthetase; 2) it is difficult to maintain a blood level of asparaginase sufficient to reduce the blood concentration of asparagine. It would seem worthwhile to seek another way to effect the metabolism of asparagine. Although some analogs of asparagine have been studied as anti-tumor or anti-leukemic agents there has not been a systematic search for compounds which interfere with either the biosynthesis or utilization of asparagine. The proposed research is aimed at uncovering such compounds. We propose to prepare aspartic acid analogs and to synthesize asparagine analogs which will compete with the asparagine in protein synthesis. We will also prepare analogs of cysteine, an amino acid needed by leukemic cells. These analogs will be studied singly and in combination with asparaginase. All of these compounds will be tested in vivo in three systems: allograft rejection in mice, mouse leukemia and (suppression of) the immune response in mice. It is anticipated that some of the compounds will be superior to asparaginase in suppression of the host response to a foreign graft, in prolonging survival in certain mouse leukemias, and in their effects on a sarcoma virus.